DESCRIPTION (Taken from application abstract): Over the last decade computational modeling has become central to neurobiology. While much of this work has focused on cellular and sub-cellular processes, the last few years have seen increasing interest in systems level models and in integrative accounts that span data from the subcellular to behavioral levels. Our proposal, in summary, is to extend existing work in parallel discrete event simulation (PDES) and integrate it with existing work on compartmental modeling environments, to produce a software environment which has comprehensive support for modeling large scale, highly structured networks of biophysically realistic cells; and which can efficiently exploit the full range of parallel platforms, including the largest parallel supercomputers, for simulation of these network models, which integrate information about the nervous system from sub-cellular to the whole-brain level. Because of the scale of the models needed at this level of integration, advanced parallel computing is required. The critical technical insight upon which this work rests is that neuronal modeling at the systems level can often be reduced to a form of discrete event simulation in which single cells are node functions and voltage spikes are events. Three neuroscience modeling projects, will mold, test, and utilize these new capabilities in investigations of system-level models of the nervous system which integrate behavioral, anatomical and physiological data on a scale that exceeds current simulation capabilities. In collaboration with computer scientists at Pittsburgh Supercomputing Center and UCLA, neuroscientists at University of Virginia, the Born-Bunge Foundation, Antwerp, and the Salk Institute, and developers of the NEURON and GENESIS packages, these tools will be developed and made available to the neuroscience community. The software development aims include 1) investigation of a portable, PDES system capable of running efficiently on diverse parallel platforms, 2) development of interfaces to the PDES for NEURON and GENESIS allowing models developed in those packages to be scaled up, 3) investigation of a network specification language for neuronal models, and associated a visualization interface, to facilitate investigation of systems-level models, 4) sufficiently robust and well-documented software for download and installation at other sites. The three neuroscience projects will guide development of the software tools and use the tools for investigation of large-scale models of cerebellum, hippocampus and thalamocortical circuits.